Synthesis of a small library of diketopiperazines as potential inhibitors of calpain

A small library of 2,5-diketopiperazines based on previously reported calpain inhibitors was synthesized. In addition, a concise total synthesis of the structurally related natural product phevalin (2) was accomplished. Despite literature reports that some of the compounds prepared were calpain inhibitors, none of the library members were found to have significant activity against recombinant human calpain I.